ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

Mao, Liyuan; Zhan, Yan-yan; Wu, Bin; Yu, Qiang; Xu, Liang; Hong, Xin; Zhong, Linhai; Mi, Panying; Li, Xiao; Wang, Xinquan; Cao, Hanwei; Zhang, Wenqing; Chen, Binbin; Xiang, Jingzhou; Mei, Kunrong; Radhakrishnan, Ravi; Guo, Wei; Hu, Tianhui

doi:10.1038/s41467-019-13923-7

Cited by 46 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…267 In highly metastatic cells, metastasis suppressors are usually downregulated in comparison with primary tumor cells. 265,268,269 In the past decade, a significant number of metastasis suppressors have been identified (Fig. 7).…”

Section: Colonizationmentioning

confidence: 99%

Molecular principles of metastasis: a hallmark of cancer revisited

Fares

Khachfe

et al. 2020

Sig Transduct Target Ther

1,538

935

View full text Add to dashboard Cite

Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.

show abstract

Section: Colonizationmentioning

confidence: 99%

Molecular principles of metastasis: a hallmark of cancer revisited

Fares

Khachfe

et al. 2020

Sig Transduct Target Ther

1,538

935

View full text Add to dashboard Cite

show abstract

“…Both Exo70 and Sec10 lays on SC2 while Sec6 is present in SC1, therefore our western blot analysis to Sec6 and Sec10 is suitable to evaluate the assembly of the exocyst. This approach has been used before on biochemical experiments with a similar aiming on exocyst assembly and activity [15,16,52,74]. The exocyst is a complex widely distributed intracellularly [12,21], so immunoprecipitating Exo70 in hippocampal protein extracts would add several difficulties in assessing the particular assembly on synapses.…”

Section: Discussionmentioning

confidence: 99%

“…Exo70 has been proposed as the nucleating factor of the exocyst complex establishing the site where the complex should be directed [21,[49][50][51]. Also, the level of assembly of the complex through Exo70 denotes its activity on exocytosis [15,16,52]. Therefore, we sought to determine if the assembly of the exocyst complex is altered on mTBI mice.…”

Section: Exocyst Assembly Following Mild Traumatic Brain Injurymentioning

confidence: 99%

See 1 more Smart Citation

Exo70 intracellular redistribution after repeated mild traumatic brain injury

2021

View full text Add to dashboard Cite

Background Exo70 is a subunit of the greater exocyst complex, a collection of proteins that oversees cellular membrane addition and polarized exocytosis by acting as a tethering intermediate between the plasma membrane and newly synthesized secretory vesicles. Although Exo70 function has been implicated in several developmental events including cytokinesis and the establishment of cell polarity, its role in neuropathologies is poorly understood. On the other hand, traumatic brain injury is the result of mechanical external force including contusion, fast acceleration, and expansive waves that produce temporal or permanent cognitive damage and triggers physical and psychosocial alterations including headache, memory problems, attention deficits, difficulty thinking, mood swings, and frustration. Traumatic brain injury is a critical health problem on a global scale, constituting a major cause of deaths and disability among young adults. Trauma-related cellular damage includes redistribution of N-methyl-D-aspartate receptors outside of the synaptic compartment triggering detrimental effects to neurons. The exocyst has been related to glutamate receptor constitutive trafficking/delivery towards synapse as well. This work examines whether the exocyst complex subunit Exo70 participates in traumatic brain injury and if it is redistributed among subcellular compartments Results Our analysis shows that Exo70 expression is not altered upon injury induction. By using subcellular fractionation, we determined that Exo70 is redistributed from microsomes fraction into the synaptic compartment after brain trauma. In the synaptic compartment, we also show that the exocyst complex assembly and its interaction with GluN2B are increased. Finally, we show that the Exo70 pool that is redistributed comes from the plasma membrane. Conclusions The present findings position Exo70 in the group of proteins that could modulate GluN2B synaptic availability in acute neuropathology like a traumatic brain injury. By acting as a nucleator factor, Exo70 is capable of redirecting the ensembled complex into the synapse. We suggest that this redistribution is part of a compensatory mechanism by which Exo70 is able to maintain GluN2B partially on synapses. Hence, reducing the detrimental effects associated with TBI pathophysiology.

show abstract

“…Moreover, cirMUC16 could also function as a ceRNA for miR-199a-5p and relieve its inhibitory on Beclin-1 and RUNX1 [ 81 ]. Nevertheless, in breast cancer, the expression of autophagy-related genes negatively correlates with pre-metastasis signatures, and thereof restricts tumor metastasis [ 105 , 106 ].…”

Section: An Overview Of Autophagy-regulated Cancer Metastasis and mentioning

confidence: 99%

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Zhang

Lü

2020

Cancers

View full text Add to dashboard Cite

Chemoresistance and metastasis are the main causes of treatment failure and unfavorable outcome in cancers. There is a pressing need to reveal their mechanisms and to discover novel therapy targets. Autophagy is composed of a cascade of steps controlled by different autophagy-related genes (ATGs). Accumulating evidence suggests that dysregulated autophagy contributes to chemoresistance and metastasis via competing endogenous RNA (ceRNA) networks including lncRNAs and circRNAs. ceRNAs sequester the targeted miRNA expression to indirectly upregulate ATGs expression, and thereof participate in autophagy-mediated chemoresistance and metastasis. Here, we attempt to summarize the roles of ceRNAs in cancer chemoresistance and metastasis through autophagy regulation.

show abstract

ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

Cited by 46 publications

References 29 publications

Molecular principles of metastasis: a hallmark of cancer revisited

Molecular principles of metastasis: a hallmark of cancer revisited

Exo70 intracellular redistribution after repeated mild traumatic brain injury

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Contact Info

Product

Resources

About